CCL2 regulated by the CTBP1-AS2/miR-335-5p axis promotes hemangioma progression and angiogenesis.

CONTEXT: Hemangioma (HA) is a benign vascular neoplasm that can lead to permanent scarring. C-C motif chemokine ligand 2 (CCL2) plays a crucial role in facilitating growth and angiogenesis during HA progression. However, the mechanism regulating CCL2 in HA remains poorly elucidated. OBJECTIVE: To elucidate the mechanism regulating CCL2 in HA. METHODS: Quantitative real-time polymerase chain reaction (RT-qPCR) was employed to determine the expression levels of CCL2, long noncoding RNA (lncRNA) CTBP1 divergent transcript (CTBP1-AS2), and microRNAs (miRNAs). Proliferation, migration, invasion, and angiogenic abilities of human HA endothelial cells (HemECs) were assessed using cell counting kit-8 (CCK-8), colony formation, flow cytometry, transwell, and tube formation assays. Bioinformatics analysis, RNA pull-down, and luciferase reporter assays were conducted to investigate whether CCL2 targets miR-335-5p. Additionally, rescue experiments were performed in this study. RESULTS: CCL2 expression was markedly upregulated in HemECs. CCL2 promoted HA cell proliferation, migration, invasion, and angiogenesis while inhibiting apoptosis. CCL2 was directly targeted by miR-335-5p. Additionally, we found that CTBP1-AS2 could function as a competing endogenous RNA (ceRNA) to sponge miR-335-5p, thereby upregulating CCL2. CONCLUSION: Our findings suggest that targeting the CTBP1-AS2/miR-335-5p/CCL2 axis may hold promise as a therapeutic strategy for HA.

Single-atom and cluster catalysts for thermocatalytic ammonia synthesis at mild conditions.

Ammonia (NH3) is closely related to the fields of food and energy that humans depend on. The exploitation of advanced catalysts for NH3 synthesis has been a research hotspot for more than one hundred years. Previous studies have shown that the Ru B5 sites (step sites on the Ru (0001) surface uniquely arranged with five Ru atoms) and Fe C7 sites (iron atoms with seven nearest neighbors) over nanoparticle catalysts are highly reactive for N2-to-NH3 conversion. In recent years, single-atom and cluster catalysts, where the B5 sites and C7 sites are absent, have emerged as promising catalysts for efficient NH3 synthesis. In this review, we focus on the recent advances in single-atom and cluster catalysts, including single-atom catalysts (SACs), single-cluster catalysts (SCCs), and bimetallic-cluster catalysts (BCCs), for thermocatalytic NH3 synthesis at mild conditions. In addition, we discussed and summarized the unique structural properties and reaction performance as well as reaction mechanisms over single-atom and cluster catalysts in comparison with traditional nanoparticle catalysts. Finally, the challenges and prospects in the rational design of efficient single-atom and cluster catalysts for NH3 synthesis were provided.

Effects of an intraoperative intravenous Bolus Dose of Dexmedetomidine on postoperative catheter-related bladder discomfort in male patients undergoing transurethral resection of bladder tumors: a randomized, double-blind, controlled trial.

PURPOSE: To investigate whether the effect of intravenous bolus doses of dexmedetomidine on postoperative catheter-related bladder discomfort (CRBD) was dose-dependent in male patients undergoing transurethral resection of bladder tumors (TURBT). METHODS: The study protocol was registered at the Chinese Clinical Trial Registry (ChiCTR 2,000,034,657, date of registration: July 14, 2020). Adult male patients were randomized to one of four groups: placebo (Group C); dexmedetomidine 0.2 µg/kg (Group D 0.2); dexmedetomidine 0.5 µg/kg (Group D 0.5); or dexmedetomidine 1 µg/kg (Group D 1). The primary outcome was the incidence of moderate-to-severe CRBD at 0, 1, 6, 24, and 48 h postoperatively. RESULTS: The incidence of moderate-to-severe CRBD was significantly lower in Group D 0.5 and Group D 1 than in Group C at 0 h (13% vs. 40%, P = 0.006; 8% vs. 40%, P = 0.001), 1 h (15% vs. 53%, P < 0.001; 13% vs. 53%, P < 0.001), and 6 h (10% vs. 32%, P = 0.025; 8% vs. 32%, P = 0.009) postoperatively. Compared with baseline, both the MAP and HR were significantly lower in Group D 1 at 1 min ([94 ± 15] vs. [104 ± 13] mm Hg, P = 0.003; [64 ± 13] vs. [73 ± 13] bpm, P = 0.001) and 30 min ([93 ± 10] vs. [104 ± 13] mm Hg, P < 0.001; [58 ± 9] vs. [73 ± 13] bpm, P < 0.001) postextubation. CONCLUSION: The effect of intravenous bolus doses of dexmedetomidine on postoperative CRBD was dose-independent, whereas intravenous administration of 0.5 µg/kg dexmedetomidine reduced the early postoperative incidence of CRBD with minimal side effects. TRIAL REGISTRATION: Clinical trial number and registry URL: ChiCTR 2,000,034,657, http://www.chictr.org.cn , date of registration: July 14, 2020.

Antitumor Effects of ß-Elemene Through Inducing Autophagy-Mediated Apoptosis in Ewing Sarcoma Family Tumor Cells.

Ewing sarcoma family tumors (ESFTs) are a group of aggressive tumors mainly affecting children and young people. A compound derived from Curcuma wenyujin plant or lemon grass, ß-elemene, has exhibited antitumor effects to ESFT cells, the mechanism of which remains to be clarified further. Autophagy is involved in the antitumor effects of various drugs, whereas the role of autophagy in the antitumor effects of ß-elemene persists controversial. Herein we found that ß-elemene treatment inhibited the viability of ESFT cells in a dose-dependent manner. The increase of LC3-II level and the decrease of p62 level were observed in ß-elemene-treated cells, as well as the increase of autolysosomes, which indicated the promotion of autophagic flux. Sequentially the autophagy inhibition using 3-MA treatment or ATG5 depletion significantly reversed the viability repression and apoptosis induction by ß-elemene treatment. In addition, autophagy was found to be important in the toxic effects induced by the combination treatment of ß-elemene and IGF1R inhibition in ESFT cells. Our data suggested an essential role of autophagy in ß-elemene-induced apoptosis in ESFT cells, which is anticipated to provide novel insights to the development of ESFT treatments.

Effects of S-ketamine on Postoperative Recovery Quality and Inflammatory Response in Patients Undergoing Modified Radical Mastectomy.

INTRODUCTION: S-ketamine plays an important role in reducing postoperative pain, but its impact on the quality of recovery in breast cancer has not been clarified. We designed this trial to explore the effects of s-ketamine on the quality of postoperative recovery and inflammatory response in modified radical mastectomy. METHODS: A total of 138 patients were randomly assigned to group C (group control), group K1 (group of s-ketamine dose 1) and group K2 (group of s-ketamine dose 2). Groups K1 and K2 were given 0.1 mg/kg, 0.2 mg/kg s-ketamine intravenous (IV) after induction, followed by 0.1 mg/kg/h or 0.2 mg/kg/h continuous intravenous infusion, respectively. Group C received the same volume of saline. A 40-item Quality of Recovery Questionnaire (QoR-40) was used to assess the quality of recovery at 24 h postoperatively. Changes in inflammatory markers, nociceptive thresholds, and the occurrence of adverse events were recorded at 24 h postoperatively. RESULTS: The QoR-40 scores at 24 h postoperatively were higher in group K2 [182.00 (179.00-185.00)] compared to group K1 [174.00 (169.50-180.50)] and group C [169.00 (163.75-174.25)] (group K2 vs. group K1, P < 0.001; group K2 vs. group C, P < 0.001). At 24 h postoperatively, the neutrophil count, NLR (neutrophil-lymphocyte ratio), and CRP (C-creative protein) were all significantly lower in group K2 than group C(P < 0.05), no differences were observed between group K1 and C(P > 0.05), group K1 and K2(P > 0.05), respectively. There was no significant difference in the incidence of adverse effects among the three groups (P > 0.05). CONCLUSIONS: A high dose of s-ketamine improved the quality of recovery at 24 h after surgery, as well as alleviated the inflammatory response without increasing the incidence of adverse effects.

Association between driving pressure and postoperative pulmonary complications in patients undergoing lung resection surgery: A randomised clinical trial.

BACKGROUND: It is uncertain whether an association exists for decreases in driving pressure and the occurrence of postoperative pulmonary complications (PPCs) in patients undergoing selective lung resection surgery. Thus, we designed this study to determine whether the positive end-expiratory pressure (PEEP) titration to the lowest driving pressure compared with conventional low PEEP level during one-lung ventilation (OLV) in patients undergoing selective lung resection surgery decreases PPCs. METHODS: This single-centre, randomised trial approved by the Ethical Committee of the Sun Yat-Sen University Cancer Center involved patients who signed written consent. Patients were randomised to the PEEP titration to the lowest driving pressure group (n = 104), or to the conventional low level of PEEP group (n = 103), consisting a PEEP level of 4 cm H2O during OLV. All patients received volume-controlled ventilation with a tidal volume of 6 mL/kg of predicted body weight. The primary outcome was defined as positive if 4 or more of eight Melbourne Group Scale (MGS) variables developed within the first 3 days after surgery. The incidence of major PPCs occurring during postoperative 7 days was also recorded. RESULTS: Among 222 patients who were randomised, 207 (93%) completed the trial (109 men [53%]; mean age, 56.9 years). The primary outcome occurred in 4 of 104 patients (4%) in the PEEP titration to the lowest driving pressure group compared with 13 of 103 patients (13%) in the conventional low level of PEEP group (risk ratio, 0.32 [95% CI, 0.10-0.90]; P = 0.021). CONCLUSIONS: Among patients undergoing selective lung surgery, intraoperative OLV with PEEP titration to the lowest driving pressure compared with conventional low PEEP level (4 cm H2O) significantly reduced PPCs within the first 3 postoperative days, however, did not significantly reduce PPCs within the first 7 postoperative days.

Application effect of rapid diagnostic techniques in pulmonary tuberculosis in Shaanxi, 2016-2020 / 中国热带医学

@#Abstract: Objective To analyze the application effect of rapid diagnostic techniques in Shaanxi from 2016 to 2020,and to provide basis for further optimizing the process of tuberculosis detection and formulating prevention and control strategies. Methods A total of 104 437 cases of tuberculosis patients registered in Shaanxi Province from 2016-2020 were exported from the Tuberculosis Information Management System (The subsystem of China Disease Prevention and Control Information System) according to first management unit, and the laboratory test results of sputum smear, sputum culture and molecular tests were collected to statistically analyzed the positive rate of etiology, sputum smear, sputum culture, molecular biology testing rate, and indicators of positive testing rate of tuberculosis patients. Results From 2016 to 2020, the etiology�positive rate of tuberculosis in Shaanxi province were 13.49% (2 664/19 754), 22.68% (5 081/22 401), 35.99% (8 232/22 876), 48.14% (10 438 / 21 682), 52.65% (9 332 / 17 724), respectively, with an increasing trend (χ2 trend=9 473.12, P<0.001) year by year; the proportion of molecular tests positive only in etiology-positive pulmonary tuberculosis (PTB) were 0 (0/2 664), 0.16% (8/5 081), 15.44% (1 271/8 232), 27.58% (2 879/10 438), 31.52% (2 941/9 332), respectively, with an increasing trend year by year (χ2 trend=2 971.44, P<0.001); the molecular test rates of the 5 years were 0.01% (2 / 19 754), 0.38%(85 / 22 401), 21.11% (4 828/22 876), 52.42%(11 365/21 682), 55.18%(9 780/17 724), respectively, with an increasing trend year by year (χ2 trend = 28 269.23, P<0.001). The rate of molecular test in sputum smear-negative was 22.72%(17 976 / 79 130). The proportion of patients with only molecular test-positive was 33.43% (4 032/12 062) in municipal designated hospitals, and 11.99%(2 279/ 19 014) in county-level designated hospitals, the difference was statistically significant (χ2 =2 096.46, P<0.001). Conclusions The rate of molecular biology testing in Shaanxi Province from 2016 to 2020 showed a year-on-year increase. Through the application of rapid molecular tests, the etiology-positive rates of tuberculosis have been increased significantly,but the current molecular test detection rate is not high compared with other provinces, especially in county-level designated hospitals and smear-negative patients, so we should make a big promotion in application of rapid molecular technique.

Comparison of esketamine versus dexmedetomidine for attenuation of cardiovascular stress response to double-lumen tracheal tube intubation: a randomized controlled trial.

Introduction: The insertion of a double-lumen tracheal tube may cause a transient but more intense sympathetic response. We examined the effects of esketamine vs. dexmedetomidine as an adjuvant to anesthesia induction to blunt double lumen tracheal (DLT) intubation induced cardiovascular stress response. Methods: In a randomized, double-blind trial, 78 adult patients scheduled for elective thoracotomy under general anesthesia requiring DLT intubation were enrolled. The patients were randomly divided into three groups: each group received one of the following drugs prior to induction of anesthesia: dexmedetomidine 0.8 µg/kg (Group A), esketamine 0.5 mg/kg (Group B), or normal saline (group C). The primary outcome was the incidence of a DLT intubation-related cardiovascular stress response, defined as an increase in mean arterial pressure or heart rate of >30% above the baseline values. The secondary outcomes were changes in hemodynamic and cardiac function. Results: The incidence of the response to cardiovascular stress was 23.1%, 30.8%, and 65.4% in groups A, B, and C, respectively. There was a significant decrease in intubation response in groups A and B in comparison with group C (P < 0.01); however, there was no significant difference between group A and group B (P > 0.05). Following the drug infusion and the induction of anesthesia, there was a significant decrease in HR and cardiac output in group A compared with group B. In contrast, no significant differences were observed in the left ventricular ejection fraction or in stroke volume between the three groups during induction of anesthesia. Discussion: Esketamine 0.5 mg/kg and dexmedetomidine 0.8 µg/kg attenuate cardiovascular stress responses related to DLT intubation. As adjuvants to etomidate induction, they do not impair cardiac function (ChiCTR1900028030).

[Electroacupuncture promotes gastrointestinal motility by activating autophagy of Cajal interstitial cells via downregulating PI3K/Akt/mTOR signaling pathway in stomach of diabetic gastro-paresis rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Zusanli" (ST36), "Sanyinjiao" (SP6) and "Liangmen" (ST21) on gastrointestinal motility, blood glucose content and expression of autophagy-related proteins 1 light chain 3 (LC3), p62, phosphatidyli-nositol-3 kinase (PI3K), protein kinase B (Akt), p-Akt and mammalian target protein of rapamycin (mTOR) of interstitial cells of Cajal (ICCs) in the cultured gastric antrum cells in diabetic gastroparesis (DGP) rats, so as to reveal its mechanisms underlying improvement of DGP. METHODS: A total of 45 Sprague Dawley (SD) rats were randomly divided into blank control, model, EA, medication (3-methyladenine, 3-MA) and EA+3-MA groups, with 9 rats in each group. The DGP model was established by intraperitoneal injection of 2% streptozotocin (STZ) combined with high-fat and high sugar diet for 8 weeks. The gastric emptying rate was measured by using gavage of phenol red (to measure the propelling length of the phenol red/total length of small intestine ×100%). The symptom score (mental state, coat color and luster, behavior and activity, stool traits) of rats was observed every week and the blood glucose content was measured by using a glucometer. EA (20 Hz/100 Hz, 2 mA) was applied to unilateral ST36, SP6 and ST21 alternatively for 15 min, once daily, 5 days a week for 3 weeks. Rats of the 3-MA and 3-MA+EA groups received intraperitoneal injection of 3-MA (30 mg·kg-1·d-1, 10 mg/mL), once daily, 5 days a week for 3 weeks. After 15 days' intervention, the rats were operated for gastric emptying rate test, specimen collection, isolation, and culture of primary ICCs. The expression levels of microtubule associated protein LC3, p62, PI3K, Akt, p-Akt and mTOR of ICCs of cultured gastric antrum cells were detected using Western blot, and the number of autophagosomes in ICC of gastric antrum was observed under transmission electron microscope. RESULTS: Compared with the blank control group, the symptom score, blood glucose, and the expression levels of p62, class Ⅰ PI3K, Akt, p-Akt and mTOR proteins were increased significantly (P<0.01), while the gastric emptying rate and ratio of LC3Ⅱ/LC3Ⅰ and the expression level of class Ⅲ PI3K protein were significantly decreased (P<0.05, P<0.01) in the model group. In comparison with the model group, the increase of symptom score, blood glucose, and expression levels of p62, class Ⅰ PI3K, Akt, p-Akt and mTOR proteins and the decrease of gastric empty rate and LC3Ⅱ/LC3Ⅰ ratio and the expression level of class Ⅲ PI3K protein were all reversed in both EA and EA+3-MA groups (P<0.05, P<0.01), rather than in the 3-MA group. In addition, 3-MA also reversed modeling-induced increase of class Ⅰ PI3K, Akt, p-Akt and mTOR proteins expression (P<0.01). No significant differences were found between the EA and EA+3-MA in downregulating the levels of symptom score and blood glucose content, and in upregulating gastric empty rate(P>0.05). The effect of EA was notably superior to that of EA+3-MA in upregulating the ratio of LC3Ⅱ/LC3Ⅰ and the expression level of class Ⅲ PI3K protein, and in downregulating the expression of p62, class Ⅰ PI3K, Akt, p-Akt and mTOR proteins (P<0.05, P<0.01). The findings of transmission electron microscopy showed obvious swelling, breakage of some mitochondrial cristae in the ICC cells of antrum and no autophagosomes in the model group and 3-MA group, which was milder in the damage of mitochondrial cristae and marked increase in the autophagosomes in both EA and EA+3-MA groups. CONCLUSION: EA can improve the gastrointestinal motility and symptoms in DGP rats, which may be related to its functions in downregulating PI3K/Akt/mTOR signaling to promote autophagy level of ICC.

ß-elemene Isopropanolamine Derivative LXX-8250 Induces Apoptosis Through Impairing Autophagic Flux via PFKFB4 Repression in Melanoma Cells.

Melanoma is a highly aggressive skin cancer and accounts for most of the skin cancer-related deaths. The efficacy of current therapies for melanoma remains to be improved. The isopropanolamine derivative of ß-elemene LXX-8250 was reported to present better water solubility and stronger toxicity to tumor cells than ß-elemene. Herein, LXX-8250 treatment showed 4-5-fold more toxicity to melanoma cells than the well-known anti-melanoma drug, Dacarbazine. LXX-8250 treatment induced apoptosis remarkably, which was caused by the impairment of autophagic flux. To clarify the molecular mechanism, microarray analyses were conducted, and PFKFB4 expression was found to be suppressed by LXX-8250 treatment. The cells overexpressed with PFKFB4 exhibited resistance to apoptosis induction and autophagic flux inhibition by LXX-8250 treatment. Moreover, LXX-8250 treatment suppressed glycolysis, to which the cells overexpressed with PFKFB4 were tolerant. LXX-8250 treatment inhibited the growth of melanoma xenografts and suppressed PFKFB4 expression and glycolysis in vivo. Taken together, LXX-8250 treatment induced apoptosis through inhibiting autophagic flux and glycolysis in melanoma cells, which was mediated by suppression of PFKFB4 expression. The study provides a novel strategy to melanoma treatment.

Evaluation of digestibility differences for apple polyphenolics using in vitro elderly and adult digestion models.

We evaluated the in vitro digestibility of apple polyphenols mimicking elderly and adult digestion models (dynamic and static systems). The digestibility of total apple polyphenols in small intestine was much higher in the adult dynamic system (62 µg/100 g fresh apple) compared to the static system (20 µg/100 g fresh apple) and elderly dynamic digestion conditions (33 µg/100 g fresh apple). Elderly in vitro static digestion showed better antioxidant activity than the adult system (OH and ABTS+ methods). Thus, the in vitro dynamic digestion system can more truly reflect the digestion of apple polyphenols than static digestion system. Moreover, elderly digestion conditions negatively influenced the digestibility of apple polyphenols including chlorogenic acid, epicatechin, phlorizin, rutin, phloretin, hyperoside, proanthocyanidin B2, and quercetin. Hence, appropriate selection of in vitro digestion models for elderly is a prerequisite to exploring the digestibility of phytochemicals for the development of functional food products for elderly.

Peroxiredoxin 6 mediates the protective function of curcumin pretreatment in acute lung injury induced by serum from patients undergoing one-lung ventilation in vitro.

BACKGROUND: Curcumin has attracted much attention due to its wide range of therapeutic effects. In this study, we used serum collected from patients undergoing one-lung ventilation (OLV) to establish an in vitro acute lung injury (ALI) model to explore the potential protective mechanism of curcumin on ALI. Our study provides a new reference for the prevention and treatment of ALI induced by OLV. METHODS: A549 cells were treated with 20% serum from patients undergoing OLV to establish an in vitro ALI model. Curcumin, at a dose of 40 µg/ml, was administered two hours prior to this model. The levels of inflammation and oxidative stress markers were observed by Western blot, qRT-PCR, ELISA and reactive oxygen species assay. Additionally, the expression of peroxiredoxin 6 (Prdx6) and proteins involved in the NF-κB signaling pathway was evaluated. RESULTS: Twenty percent of serum collected from patients undergoing OLV downregulated the expression of Prdx6, leading to the activation of the NF-κB signaling pathway, which was associated with the subsequent overproduction of inflammatory cytokines and reactive oxygen species. Pretreatment with curcumin restored Prdx6 downregulation and inhibited NF-κB pathway activation by suppressing the nuclear translocation of P65, eventually reducing inflammation and oxidative stress damage in A549 cells. CONCLUSIONS: Prdx6 mediated the protective function of curcumin by inhibiting the activation of the NF-κB pathway in ALI in vitro.

Distribution of bacteriologically positive and bacteriologically negative pulmonary tuberculosis in Northwest China: spatiotemporal analysis.

Pulmonary tuberculosis (PTB) is a major health issue in Northwest China. Most previous studies on the spatiotemporal patterns of PTB considered all PTB cases as a whole; they did not distinguish notified bacteriologically positive PTB (BP-PTB) and notified bacteriologically negative PTB (BN-PTB). Thus, the spatiotemporal characteristics of notified BP-PTB and BN-PTB are still unclear. A retrospective county-level spatial epidemiological study (2011-2018) was conducted in Shaanxi, Northwest China. In total, 44,894 BP-PTB cases were notified, with an average annual incidence rate of 14.80 per 100,000 persons between 2011 and 2018. Global Moran's I values for notified BP-PTB ranged from 0.19 to 0.49 (P < 0.001). Anselin's local Moran's I analysis showed that the high-high (HH) cluster for notified BP-PTB incidence was mainly located in the southernmost region. The primary spatiotemporal cluster for notified BP-PTB (LLR = 612.52, RR = 1.77, P < 0.001) occurred in the central region of the Guanzhong Plain in 2011. In total, 116,447 BN-PTB cases were notified, with an average annual incidence rate of 38.38 per 100,000 persons between 2011 and 2018. Global Moran's I values for notified BN-PTB ranged from 0.39 to 0.69 (P < 0.001). The HH clusters of notified BN-PTB were mainly located in the north between 2011 and 2014 and in the south after 2015. The primary spatiotemporal cluster for notified BN-PTB (LLR = 1084.59, RR = 1.85, P < 0.001) occurred in the mountainous areas of the southernmost region from 2014 to 2017. Spatiotemporal clustering of BP-PTB and BN-PTB was detected in the poverty-stricken mountainous areas of Shaanxi, Northwest China. Our study provides evidence for intensifying PTB control activities in these geographical clusters.

High miRNA-378 expression has high diagnostic values for pulmonary tuberculosis and predicts adverse outcomes.

BACKGROUND: Pulmonary tuberculosis (TB) is a chronic infectious disease. microRNA (miR)-378 is involved in TB diagnosis. This study explored the effects of miR-378 on TB patients. METHODS: A total of 126 TB patients were selected, including 63 active TB and 63 latent TB, with 62 healthy subjects as controls. Serum miR-378 expression was detected. The diagnostic value of miR-378 in TB was analyzed using the ROC curve. Immune inflammatory factor levels were detected and their correlations with miR-378 expression were analyzed. The drug resistance of active TB patients was recorded after standard treatment. miR-378 expression in drug-resistant TB patients was detected. The effects of miR-378 on adverse outcome incidence were analyzed. RESULTS: miR-378 expression was highly expressed in TB and the expression was higher in the active group than the latent group. Serum miR-378 expression > 1.490 had high sensitivity and specificity in TB diagnosis. miR-378 expression was correlated with TB clinical indexes. IL-4, IL-6, and IL-1ß levels were highly expressed, while IFN-γ, TNF-α, and IL-12 levels were lowly expressed in TB patients. Serum miR-378 level in the active group was positively correlated with serum IL-4, IL-6, and IL-1ß, and negatively correlated with serum IFN-γ, TNF-α, and IL-12 concentrations. miR-378 expression was downregulated in the TB treated, single (SDR TB) and multi-drug resistance (MDR TB) groups, the miR-378 expression in SDR TB and MDR TB groups was higher than the TB treated group and lower in the SDR TB group than the MDR TB group. High miR-378 expression predicted higher adverse outcome incidence. CONCLUSIONS: High miR-378 expression assisted TB diagnosis and predicted adverse outcomes.

[Application of thin free lateral femoral circumflex artery perforator flap in repair of scar contracture deformity in hand and foot].

OBJECTIVE: To explore the effectiveness of thin free lateral femoral circumflex artery perforator flaps that dissected under the superficial fascia in repair of scar contracture deformity in hand and foot. METHODS: Between January 2017 and October 2020, 15 patients with scar contracture deformity in hand or foot were admitted. There were 9 males and 6 females; aged 6-42 years, with a median age of 23 years. Scar contracture lasted from 1 to 21 years, with a median of 13 years. There were 11 cases of scar contracture deformities in the hands and 4 cases in the feet, all of which showed different degrees of hand and foot joint dysfunction. After the scar contracture was released, the size of wounds ranged from 6 cm×4 cm to 9 cm×8 cm, including 12 cases with exposure of blood vessels, nerves, or tendons, and 4 cases with tendon defects. A thin free lateral circumflex femoral artery perforator flap that dissected under the superficial fascia was used to repair the wound. The size of flap ranged from 6.0 cm×5.0 cm to 10.0 cm×8.5 cm. Fascia strips were used to reconstruct tendons and the donor sites were sutured directly. RESULTS: The venous vascular crisis occurred in 1 flap, and the flap survived successfully after treatment. The rest flaps survived well, and the wounds healed by first intention. All incisions at donor sites healed by first intention. All patients were followed up 6-12 months after operation, with an average of 9 months. The flaps were in good shape and texture. The functions of the affected hand had been restored to a large extent. According to the upper limb function evaluation standard of the Society of Hand Surgery of the Chinese Medical Association, 7 cases were excellent and 4 cases were good. The deformity of the toe joint of the affected foot significantly improved. No muscular hernia, sensory numbness, or other complications occurred at the donor sites. CONCLUSION: The thin free lateral femoral circumflex artery perforator flap that dissected under the superficial fascia is an effective method to repair scar contracture deformity of hand and foot with well appearance, good function recovery, and less complication of the donor sites.

[Repair of complex wounds of limbs with free lobed perforator flaps].

OBJECTIVE: To explore the effectiveness of free lobed perforator flaps in repairing of complex wounds of limbs. METHODS: Between January 2018 and January 2021, 10 patients with complex wounds of limbs were admitted. There were 7 males and 3 females, aged from 32 to 64 years, with an average age of 45 years. There were 4 cases of traffic accident injuries, 3 cases of machine strangulation injuries, 1 case of machine crush injury, and 2 cases of heavy object crush injuries. There were 5 cases of upper limb wounds and 5 cases of lower limb wounds. The size of wounds ranged from 11 cm×10 cm to 25 cm×18 cm. The wounds were repaired with tri-lobed flaps of the descending branch of the lateral femoral circumflex artery in 7 cases, four-lobed flaps in 2 cases, and with tri-lobed flaps of the descending branch of the lateral femoral circumflex artery combined with oblique branch in 1 case. The size of flaps ranged from 12.0 cm×10.5 cm to 28.0 cm×12.0 cm. The donor sites were sutured directly in 9 cases and repaired with superficial iliac circumflex artery perforator flap in 1 case. RESULTS: Sinus formed at the edge of the flap in 1 patient, which healed after dressing change and drainage; other flaps survived well, and the wounds healed by first intention. The skin flap at donor site survived, and the incisions healed by first intention. All patients were followed up 6-24 months (mean, 11 months). All flaps had good appearance and function, and linear scars were left at the donor site without obvious complications. CONCLUSION: Free lobed perforator flap is an alternative method to repair complex wounds of limbs with high safety, good effectiveness, and less complications.

PGK1 represses autophagy-mediated cell death to promote the proliferation of liver cancer cells by phosphorylating PRAS40.

Autophagy predominantly promotes cell survival by recycling cell components, while it kills cells in specific contexts. Cell death related to autophagy plays important roles in multiple physiological and pathological situations including tumorigenesis, and the mechanism needs to be defined further. PRAS40 was found to be crucial in various cancers, and phosphorylation was reported to be involved in autophagy inhibition in monocytes. However, the detailed role of PRAS40 in autophagy and the relationship to tumorigenesis remain largely unknown. Herein we screened the binding partners of PRAS40, and found that PRAS40 interacted with Phosphoglycerate kinase 1 (PGK1). PGK1 phosphorylated PRAS40 at Threonine 246, which could be inhibited by blocking the interaction. Both in vitro and in vivo results revealed that PRAS40 mediated PGK1-induced cell growth. By tracing the mechanism, we found that PGK1 suppressed autophagy-mediated cell death, in which PRAS40 was crucial. Thus PGK1 phosphorylates PRAS40 to repress autophagy-mediated cell death under normoxia, promoting cellular proliferation. The binding of PGK1 to PRAS40 was transferred to Beclin1 under hypoxia, resulting in the increase of Beclin1 phosphorylation. These results suggest a novel model of tumorigenesis, in which PGK1 switches between repressing autophagy-mediated cell death via PRAS40 and inducing autophagy through Beclin1 according to the environmental oxygen level. Our study is anticipated to be able to offer novel insights in understanding PGK1/PRAS40 signaling hyperactivated cancers.

Effects of Etco2 on the Minimum Alveolar Concentration of Sevoflurane that Blunts the Adrenergic Response to Surgical Incision: A Prospective, Randomized, Double-Blinded Trial.

BACKGROUND: CO2 has anesthetic potency and effectively influences the circulatory system. We investigated the effects of Etco2 on the minimum alveolar concentration of sevoflurane that blunts the adrenergic response to surgical incision (MAC-BAR) in patients undergoing radical surgery for gastric carcinoma. METHODS: Ninety patients undergoing radical gastric-carcinoma surgery under general anesthesia were enrolled and randomly assigned into 3 groups. After intubation, the Etco2 in group L (n = 30), group N (n = 30), and group H (n = 30) was adjusted to 25 mm Hg ≤ Etco2 <30 mm Hg, 30 mm Hg ≤ Etco2 < 40 mm Hg, and 40 mm Hg ≤ Etco2 < 45 mm Hg, respectively, by changes in controlled ventilation. Hemodynamics and depth of anesthesia were observed before and after skin incision. The MAC-BAR of sevoflurane for each group was determined using an up-and-down sequential-allocation technique. RESULTS: To obtain 7 crossovers, 25, 26, and 26 patients were used in group L, group N, and group H, respectively. The MAC-BAR of sevoflurane using the up-and-down method for group H was significantly lower than that for group L (2.3% [95% confidence interval {CI}, 2.2-2.4] vs 2.9% [95% CI, 2.7-3.0]; difference, -0.6% [95% CI, -0.7 to -0.4], P < .001) and group N (2.3% [95% CI, 2.2-2.4] vs 2.8% [95% CI, 2.8-2.9]; difference, -0.5% [95% CI, -0.7 to -0.4], P < .001), while no significant difference was found between group L and group N (P = 1.000). CONCLUSIONS: Higher Etco2 levels (Etco2 values equal to 40 mm Hg or higher) can effectively decrease the MAC-BAR of sevoflurane in patients undergoing radical surgery for gastric carcinoma.

High-sensitivity CRP may be a marker of HDL dysfunction and remodeling in patients with acute coronary syndrome.

In patients with coronary artery disease (CAD), further increasing the level of high-density lipoprotein (HDL) cholesterol (HDL-C) as an add-on to statins cannot reduce cardiovascular risk. And it has been reported that HDL functional metric-cholesterol efflux capacity (CEC) may be a better predictor of CAD risk than HDL-C. CEC measurement is time-consuming and not applicable in clinical settings. Thus, it is meaningful to explore an easily acquired index for evaluating CEC. Thirty-six CAD patients and sixty-one non-CAD controls were enrolled in this cross-sectional study. All CAD patients had acute coronary syndrome (ACS). CEC was measured using a [3H] cholesterol loading Raw 264.7 cell model with apolipoprotein B-depleted plasma (a surrogate for HDL). Proton nuclear magnetic resonance (NMR) spectroscopy was used to assess HDL components and subclass distribution. CEC was significantly impaired in CAD patients (11.9 ± 2.3%) compared to controls (13.0 ± 2.2%, p = 0.022). In control group, CEC was positively correlated with enzymatically measured HDL-C levels (r = 0.358, p = 0.006) or with NMR-determined HDL-C levels (NMR-HDL-C, r = 0.416, p = 0.001). However, in CAD group, there was no significant correlation between CEC and HDL-C (r = 0.216, p = 0.206) or NMR-HDL-C (r = 0.065, p = 0.708). Instead, we found that the level of high-sensitivity C-reactive protein (hsCRP) was inversely associated with CEC (r = - 0.351, p = 0.036). Multiple regression analysis showed that the hsCRP level was associated with CEC after adjusting other cardiovascular risk factors and HDL-C, although the association would not reach significance if adjusting for multiple testing. NMR spectroscopy showed that HDL particles shifted to larger ones in patients with high hsCRP levels, and this phenomenon was accompanied by decreased CEC. In patients with CAD, the level of HDL-C cannot reflect HDL function. The impaired correlation between HDL-C and CEC is possibly due to an inflammation-induced HDL subclass remodeling. These hypothesis-generating data suggest that hsCRP levels, a marker of acute inflammation, may associate with HDL dysfunction in ACS subjects. Due to the design limited to be correlative in nature, not permitting causal inference and a larger, strictly designed study is still needed.

Molecular Characteristics and Drug Resistance of Mycobacterium tuberculosis Isolate Circulating in Shaanxi Province, Northwestern China.

Objective: Shaanxi is the most highly populated province with high burdens of tuberculosis in northwestern China. The aim of this study was to investigate the molecular characteristics and drug resistance of Mycobacterium tuberculosis isolates from Shaanxi province of China in 2018. Methods: Phenotypic drug susceptibility testing and spoligotyping methods were performed on 518 M. tuberculosis isolates; drug-resistant isolates were sequenced in 11 drug loci, including katG, inhA, oxyR-ahpC, rpoB, embB, rpsL, rrs1 (nucleotides 388-1084), gyrA, gyrB, rrs2 (nucleotides 1158-1674), and eis. Results: The prevalences of isoniazid, rifampicin, ethambutol, streptomycin, ofloxacin, and kanamycin resistance were 22.0%, 19.3%, 7.9%, 23.8%, 10.4%, and 3.3%, respectively. The Beijing family (82.8%) was the predominant genotype, followed by the T (9.3%), H (0.6%), CAS (0.4%), LAM (0.4%), and U (0.4%) families. The percentage of Beijing genotype in a central area (88.1%) was higher than in the south (77.3%) and the north area (80.1%) (p < 0.05), while the sex, age, and treatment history between Beijing and non-Beijing family were not statistically different. Mutation analysis found that the most prevalent mutations were katG315, rpoB531, embB306, rpsL43, gyrA94, and rrs1401; the Beijing family exhibited a high rate of isoniazid-resistant isolates carrying katG315 mutations (p < 0.05). Furthermore, compared with the phenotypic data, the sensitivities of isoniazid, rifampicin, ethambutol, streptomycin, ofloxacin, and kanamycin resistance by sequencing base on 11 loci were 85.1%, 94.0%, 53.7%, 74.8%, 77.8%, and 64.7%, respectively. Conclusions: Shaanxi has a serious epidemic of drug-resistant tuberculosis, Beijing family is the predominant genotype, and the distribution showed geographic diversity. The prevalence of Beijing genotypes has a tendency to promote the transmission of high-level isoniazid-resistant M. tuberculosis. Besides, the hot spot regions localized in the embB, rrs2, and eis gene appear not to serve as excellent biomarkers for predicting ethambutol and kanamycin resistance in Shaanxi.